Extended pain relief via high frequency spinal cord modulation, and associated systems and methods

ABSTRACT

Extended pain relief via high frequency spinal cord modulation, and associated systems and methods. A method for treating a patient in accordance with a particular embodiment includes selecting a neural modulation site to include at least one of a dorsal root entry zone and dorsal horn of the patient&#39;s spinal cord, and selecting parameters of a neural modulation signal to reduce patient pain for a period of time after ceasing delivery of the signals, the period of time being at least one tenth of one second.

CROSS-REFERENCE TO RELATED APPLICATION

The is a continuation of U.S. patent application Ser. No. 14/163,149,filed Jan. 24, 2014, which is a continuation of U.S. patent applicationSer. No. 13/308,436, filed on Nov. 30, 2011, which claims priority toU.S. Provisional Application No. 61/418,379, filed on Nov. 30, 2010,each of which are incorporated herein by reference.

TECHNICAL FIELD

The present technology is directed generally to extended pain reliefobtained via high frequency spinal cord modulation, and associatedsystems and methods.

BACKGROUND

Neurological stimulators have been developed to treat pain, movementdisorders, functional disorders, spasticity, cancer, cardiac disorders,and various other medical conditions. Implantable neurologicalstimulation systems generally have an implantable pulse generator andone or more leads that deliver electrical pulses to neurological tissueor muscle tissue. For example, several neurological stimulation systemsfor spinal cord stimulation (SCS) have cylindrical leads that include alead body with a circular cross-sectional shape and one or moreconductive rings spaced apart from each other at the distal end of thelead body. The conductive rings operate as individual electrodes and, inmany cases, the SCS leads are implanted percutaneously through a largeneedle inserted into the epidural space, with or without the assistanceof a stylet.

Once implanted, the pulse generator applies electrical pulses to theelectrodes, which in turn modify the function of the patient's nervoussystem, such as by altering the patient's responsiveness to sensorystimuli and/or altering the patient's motor-circuit output. In paintreatment, the pulse generator applies electrical pulses to theelectrodes, which in turn can generate sensations that mask or otherwisealter the patient's sensation of pain. For example, in many cases,patients report a tingling or paresthesia that is perceived as morepleasant and/or less uncomfortable than the underlying pain sensation.While this may be the case for many patients, many other patients mayreport less beneficial effects and/or results. Accordingly, thereremains a need for improved techniques and systems for addressingpatient pain.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a partially schematic illustration of an implantable spinalcord modulation system positioned at the spine to deliver therapeuticsignals in accordance with several embodiments of the presentdisclosure.

FIG. 1B is a partially schematic, cross-sectional illustration of apatient's spine, illustrating representative locations for implantedlead bodies in accordance with embodiments of the disclosure.

FIG. 2A is a graph illustrating representative patient VAS scores as afunction of time for multiple patients receiving therapy in accordancewith embodiments of the disclosure.

FIG. 2B is a graph illustrating normalized pain scores for the patientsidentified in FIG. 2A, during an initial post-trial period.

FIG. 3 is a partially schematic, isometric illustration of an animalspinal cord segment and associated nerve structures, used to demonstratetechniques in accordance with the present disclosure.

FIG. 4 is a graph illustrating stimulus and response characteristics asa function of time for an animal receiving noxious electricalstimulation in accordance with an embodiment of the disclosure.

FIGS. 5A-5E illustrate response data for an animal receiving noxiouselectrical stimulation and therapy in accordance with an embodiment ofthe disclosure.

FIGS. 6A-6F illustrate animal response data for animals receivingnoxious pinch stimuli in accordance with another embodiment of thedisclosure.

FIG. 7 is a graphical illustration comparing modulation amplitudeeffects for standard SCS with those for the presently disclosedtechnology.

DETAILED DESCRIPTION 1.0 Introduction

The present technology is directed generally to spinal cord modulationand associated systems and methods for inhibiting or otherwise reducingpain via waveforms with high frequency elements or components (e.g.,portions having high fundamental frequencies), generally with reduced oreliminated side effects. Such side effects can include unwanted motorstimulation or blocking, and/or interference with sensory functionsother than the targeted pain, and/or patient proprioception. Severalembodiments continue to provide pain relief for at least some period oftime after the spinal cord modulation signals have ceased. Specificdetails of certain embodiments of the disclosure are described belowwith reference to methods for modulating one or more target neuralpopulations (e.g., nerves) or sites of a patient, and associatedimplantable structures for providing the modulation. The followingsections also describe physiological mechanisms by which it is expectedthat methods in accordance with certain embodiments achieve the observedresults. Some embodiments can have configurations, components orprocedures different than those described in this section, and otherembodiments may eliminate particular components or procedures. A personof ordinary skill in the relevant art, therefore, will understand thatthe disclosure may include other embodiments with additional elements,and/or may include other embodiments without several of the featuresshown and described below with reference to FIGS. 1A-7.

In general terms, aspects of many of the following embodiments aredirected to producing a therapeutic effect that includes pain reductionin the patient. The therapeutic effect can be produced by inhibiting,suppressing, downregulating, blocking, preventing, or otherwisemodulating the activity of the affected neural population. In manyembodiments of the presently disclosed techniques, therapy-inducedparesthesia is not a prerequisite to achieving pain reduction, unlikestandard SCS techniques. It is also expected that the techniquesdescribed below with reference to FIGS. 1A-7 can produce longer lastingresults than can existing spinal cord stimulation therapies. Inparticular, these techniques can produce results that persist after themodulation signal ceases. Accordingly, these techniques can use lesspower than existing techniques because they need not require deliveringmodulation signals continuously to obtain a beneficial effect.

Several aspects of the technology are embodied in computing devices,e.g., programmed/programmable pulse generators, controllers and/or otherdevices. The computing devices on which the described technology can beimplemented may include one or more central processing units, memory,input devices (e.g., input ports), output devices (e.g., displaydevices), storage devices, and network devices (e.g., networkinterfaces). The memory and storage devices are computer-readable mediathat may store instructions that implement the technology. In manyembodiments, the computer readable media are tangible media. In otherembodiments, the data structures and message structures may be stored ortransmitted via an intangible data transmission medium, such as a signalon a communications link. Various suitable communications links may beused, including but not limited to a local area network and/or awide-area network.

2.0 Overall System Characteristics

FIG. 1A schematically illustrates a representative patient system 100for providing relief from chronic pain and/or other conditions, arrangedrelative to the general anatomy of a patient's spinal cord 191. Theoverall patient system 100 can include a signal delivery system 110,which may be implanted within a patient 190, typically at or near thepatient's midline 189, and coupled to a pulse generator 121. The signaldelivery system 110 can provide therapeutic electrical signals to thepatient during operation. In a representative example, the signaldelivery system 110 includes a signal delivery device 111 that carriesfeatures for delivering therapy to the patient 190 after implantation.The pulse generator 121 can be connected directly to the signal deliverydevice 111, or it can be coupled to the signal delivery device 111 via asignal link 113 (e.g., an extension). In a further representativeembodiment, the signal delivery device 111 can include an elongated leador lead body 112. As used herein, the terms “lead” and “lead body”include any of a number of suitable substrates and/or support membersthat carry devices for providing therapy signals to the patient 190. Forexample, the lead 112 can include one or more electrodes or electricalcontacts that direct electrical signals into the patient's tissue, suchas to provide for patient relief. In other embodiments, the signaldelivery device 111 can include structures other than a lead body (e.g.,a paddle) that also direct electrical signals and/or other types ofsignals to the patient 190.

The pulse generator 121 can transmit signals (e.g., electrical signals)to the signal delivery device 111 that up-regulate (e.g., stimulate orexcite) and/or down-regulate (e.g., block or suppress) target nerves. Asused herein, and unless otherwise noted, the terms “modulate” and“modulation” refer generally to signals that have either type of theforegoing effects on the target nerves. The pulse generator 121 caninclude a machine-readable (e.g., computer-readable) medium containinginstructions for generating and transmitting suitable therapy signals.The pulse generator 121 and/or other elements of the system 100 caninclude one or more processors 122, memories 123 and/or input/outputdevices. Accordingly, the process of providing modulation signals,providing guidance information for locating the signal delivery device111, and/or executing other associated functions can be performed bycomputer-executable instructions contained by computer-readable medialocated at the pulse generator 121 and/or other system components. Thepulse generator 121 can include multiple portions, elements, and/orsubsystems (e.g., for directing signals in accordance with multiplesignal delivery parameters), carried in a single housing, as shown inFIG. 1A, or in multiple housings.

In some embodiments, the pulse generator 121 can obtain power togenerate the therapy signals from an external power source 118. Theexternal power source 118 can transmit power to the implanted pulsegenerator 121 using electromagnetic induction (e.g., RF signals). Forexample, the external power source 118 can include an external coil 119that communicates with a corresponding internal coil (not shown) withinthe implantable pulse generator 121. The external power source 118 canbe portable for ease of use.

During at least some procedures, an external programmer 120 (e.g., atrial modulator) can be coupled to the signal delivery device 111 duringan initial procedure, prior to implanting the pulse generator 121. Forexample, a practitioner (e.g., a physician and/or a companyrepresentative) can use the external programmer 120 to vary themodulation parameters provided to the signal delivery device 111 in realtime, and select optimal or particularly efficacious parameters. Theseparameters can include the location from which the electrical signalsare emitted, as well as the characteristics of the electrical signalsprovided to the signal delivery device 111. In a typical process, thepractitioner uses a cable assembly 114 to temporarily connect theexternal programmer 120 to the signal delivery device 111. Thepractitioner can test the efficacy of the signal delivery device 111 inan initial position. The practitioner can then disconnect the cableassembly 114 (e.g., at a connector 117), reposition the signal deliverydevice 111, and reapply the electrical modulation. This process can beperformed iteratively until the practitioner obtains the desiredposition for the signal delivery device 111. Optionally, thepractitioner may move the partially implanted signal delivery element111 without disconnecting the cable assembly 114.

After a trial period with the external programmer 120, the practitionercan implant the implantable pulse generator 121 within the patient 190for longer term treatment. The signal delivery parameters provided bythe pulse generator 121 can still be updated after the pulse generator121 is implanted, via a wireless physician's programmer 125 (e.g., aphysician's remote) and/or a wireless patient programmer 124 (e.g., apatient remote). Generally, the patient 190 has control over fewerparameters than does the practitioner.

FIG. 1B is a cross-sectional illustration of the spinal cord 191 and anadjacent vertebra 195 (based generally on information from Crossman andNeary, “Neuroanatomy,” 1995 (published by Churchill Livingstone)), alongwith multiple signal delivery devices 111 (shown as signal deliverydevices 111 a-111 d) implanted at representative locations. For purposesof illustration, multiple signal delivery devices 111 are shown in FIG.1B implanted in a single patient. In actual use, any given patient willlikely receive fewer than all the signal delivery devices 111 shown inFIG. 1B.

The spinal cord 191 is situated within a vertebral foramen 188, betweena ventrally located ventral body 196 and a dorsally located transverseprocess 198 and spinous process 197. Arrows V and D identify the ventraland dorsal directions, respectively. The spinal cord 191 itself islocated within the dura mater 199, which also surrounds portions of thenerves exiting the spinal cord 191, including the ventral roots 192,dorsal roots 193 and dorsal root ganglia 194. The dorsal roots 193 enterthe spinal cord 191 at the dorsal root entry zone 187, and communicatewith dorsal horn neurons located at the dorsal horn 186. In oneembodiment, a single first signal delivery device 111 a is positionedwithin the vertebral foramen 188, at or approximately at the spinal cordmidline 189. In another embodiment, two second signal delivery devices111 b are positioned just off the spinal cord midline 189 (e.g., about 1mm. offset) in opposing lateral directions so that the two signaldelivery devices 111 b are spaced apart from each other by about 2 mm.In still further embodiments, a single signal delivery device or pairsof signal delivery devices can be positioned at other locations, e.g.,toward the outer edge of the dorsal root entry zone 187 as shown by athird signal delivery device 111 c, or at the dorsal root ganglia 194,as shown by a fourth signal delivery device 111 d. As will be describedin further detail later, it is believed that high frequency modulationat or near the dorsal root entry zone 187, and/or at or near the dorsalhorn 186 can produce effective patient pain relief, without paresthesia,without adverse sensory or motor effects, and in a manner that persistsafter the modulation ceases.

3.0 Representative Results from Human Studies

Nevro Corporation, the assignee of the present application, hasconducted several in-human clinical studies during which multiplepatients were treated with the techniques, systems and devices that aredisclosed herein. Nevro also commissioned animal studies focusing onmechanisms of action for the newly developed techniques. The humanclinical studies are described immediately below and the animal studiesare discussed thereafter.

FIG. 2A is a graph illustrating results from patients who receivedtherapy in accordance with the presently disclosed technology to treatchronic low back pain. In general, the therapy included high-frequencymodulation at the patient's spinal cord, typically between vertebrallevels T9 and T12 (inclusive), at an average location of mid T-10. Themodulation signals were applied at a frequency of about 10 kHz, and atcurrent amplitudes of from about 2.5 mA to about 3 mA. Pulse widths wereabout 35 psec., at 100% duty cycle. Further details of representativemodulation parameters are included in co-pending U.S. patent applicationSer. No. 12/765,747, filed on Apr. 22, 2010 and incorporated herein byreference. To the extent the foregoing and/or any other materialsincorporated herein by reference conflict with the present disclosure,the present disclosure controls.

The graph shown in FIG. 2A illustrates visual analog scale (“VAS”)scores for seven representative patients as a function of time during aclinical study. Individual lines for each patient are indicated withcircled numbers in FIG. 2A, and the average is indicated by the circledletter “A”. The VAS pain scale ranges from zero (corresponding to nosensed pain) to 10 (corresponding to unbearable pain). At the far leftof FIG. 2A are VAS scores taken at a baseline point in time 145,corresponding to the patients' pain levels before receiving any highfrequency modulation therapy. During a trial period 140, the patientsreceived a high frequency modulation therapy in accordance with theforegoing parameters and the patients' VAS scores dropped significantlyup to an end of trial point 146. In addition, many patients readilyreduced or eliminated their intake of pain medications, despite thenarcotic characteristics of these medications. During an initialpost-trial period 141 (lasting, in this case, four days), the patients'VAS scores increased on average after the high frequency modulationtherapy has been halted. The rate at which pain returned after the endof the trial period varied among patients, however, as will be discussedin further detail later. Following the four-day initial post-trialperiod 141 was an interim period 142 that lasted from about 45 days toabout 80 days (depending on the patient), with the average being about62 days. After the interim period 142, a four-day pre-IPG period 143commenced ending at an IPG point 144. At the IPG point 144, the patientswere implanted with an implantable pulse generator 121, generallysimilar to that described above with reference to FIG. 1A.

The VAS scores recorded at the baseline 145 and the end of the trial 146were obtained by the patients recording their levels of pain directly tothe practitioner. During the initial post-trial period 141 and thepre-IPG period 143, the patients tracked their VAS score in patientdiaries.

FIG. 2B illustrates data in the initial post-trial period 141 describedabove with reference to FIG. 2A. For each patient, the pain levelsreported in FIG. 2A as VAS scores are shown in FIG. 2B as normalized byevaluating the patient's pain level at the end of trial 146 and at theIPG point 144. Accordingly, for each patient, the normalized pain valueis zero at the end of trial 146, and 100% at the IPG point 144. As shownin FIG. 2B, the patients generally fell into two categories: a firstgroup for whom the pain scores rapidly rose from 0% to nearly 100%within a span of about one day after the end of trial 146 (representedby lines 1, 2, 3 and 5); and a second group for whom the pain increasewas more gradual, spanning several days before reaching levels above 50%(represented by lines 4, 6 and 7). Accordingly, the data indicate thatthe patients' pain levels increased compared to the levels obtained atthe end of trial 146; however, different patients re-developed pain atdifferent rates. The resolution of the data shown in FIG. 2B is not fineenough to identify precisely how long it took for the patients in thefirst group to feel a recurrence of high pain levels. However, it wasobserved by those conducting the studies that the return of the pain forall seven patients was more gradual than is typically associated withstandard SCS methodologies. In particular, practitioners havingexperience with both standard SCS and the presently disclosed technologyobserved that patients receiving SCS immediately (e.g., withinmilliseconds) experience a return of pain upon halting the SCStreatment, while the return of pain for patients receiving the presentlydisclosed therapy was more gradual. Accordingly, it is expected that thepersistence effect of the presently disclosed therapy after beingadministered for two weeks, is likely to be on the order of minutes orhours and, (for many patients), less than one day. It is also believedthat the persistence effect may depend at least in part on how long thetherapy was applied before it was halted. That is, it is expected that,within a given time period, the longer the patient receives thepresently disclosed therapy, the longer the beneficial effect lastsafter the therapy signals are halted. Accordingly, it is expected thatthe presently disclosed therapy can produce effects lasting at least onetenth of one second, at least one second, at least one minute, at leastone hour, and/or at least one day, unlike standard

SCS techniques, which typically produce effects lasting onlymilliseconds after the electrical signal ceases. In still furtherembodiments, it is expected that at least some of the lasting effectdescribed above can be obtained by reducing the intensity (e.g., thecurrent amplitude) of the therapy signal, without ceasing the signalaltogether. In at least some embodiments (whether the signal intensityis reduced to zero or to a non-zero value), it is expected that a longenough modulation period can produce a neuroplastic or other change thatcan last indefinitely, to permanently reduce or eliminate patient pain.

An expected benefit of the persistence or long term effect describedabove is that it can reduce the need to deliver the therapy signalscontinuously. Instead, the signals can be delivered intermittentlywithout significantly affecting pain relief. This arrangement can reducepower consumption, thus extending the life of an implanted battery orother power system. It is expected that the power can be cycledaccording to schedules other than the one explicitly shown in FIGS. 2Aand 2B (e.g., other than two weeks on and up to one day off before asignificant pain recurrence). The following discussion describesexpected potential mechanisms of action by which the presently disclosedtherapy operates, including expected mechanisms by which the presentlydisclosed therapy produces effects persisting after electricalmodulation signals have ceased.

4.0 Representative Results from Animal Studies

FIG. 3 is a partially schematic, isometric view of a portion of ananimal spinal cord 391 illustrative of a study that was performed on arat model to illustrate the principles described herein. Accordingly, inthis particular embodiment, the illustrated spinal cord 391 is that of arat. During this study, a noxious electrical stimulation 370 was appliedto the rat's hind paw 384. Afferent pain signals triggered by thenoxious stimulation 370 traveled along a peripheral nerve 385 to thedorsal root ganglion 394 and then to the dorsal root 393 at the L5vertebral level. The dorsal root 393 joins the spinal cord 391 at thedorsal root entry zone 387, and transmits afferent signals to a dorsalhorn neuron 383 located at the dorsal horn 386. The dorsal horn neuron383 includes a wide dynamic range (“WDR”) cell. An extracellularmicroelectrode 371 recorded signals transmitted by the dorsal hornneuron 383 to the rat's brain, in response to the noxious stimulation370 received at the hind paw 384. A therapeutic modulation signal 326was applied at the dorsal root entry zone 387, proximate to the dorsalhorn 386.

FIG. 4 is a graph illustrating neural signal amplitude as a function oftime, measured by the recording electrode 371 described above withreference to FIG. 3. FIG. 4 identifies the noxious stimulation 370itself, the dorsal horn neuron's response to A-fiber inputs 372, and thedorsal horn neuron's response to C-fiber inputs 373. The larger A-fiberstrigger an earlier response at the dorsal horn neuron than do thesmaller C-fibers. Both responses are triggered by the same noxiousstimulus 370. The rat's pain response is indicated by downward amplitudespikes. The foregoing response is a typical response to a noxiousstimulus, absent pain modulation therapy.

FIGS. 5A-5E illustrate the dorsal horn neuron response to ongoingnoxious stimuli as the applied therapy signal was altered. The signalapplied to each rat was applied at a constant frequency, which variedfrom rat to rat over a range of from about 3 kHz to about 100 kHz. Theresponse data (which were obtained from nine rats) were relativelyinsensitive to frequency over this range. During the course of thisstudy, the noxious stimuli were provided repeatedly at a constant rateof one stimulus per second over an approximately five-minute period. Atthe outset of the five-minute period, the therapy signal was turned off,resulting in a baseline response 574 a shown in FIG. 5A, and thengradually increased as shown in FIG. 5B, to a maximum intensity shown inFIG. 5C. During the period shown in FIG. 5D, the intensity of thetherapy signal was reduced, and in FIG. 5E, the therapy signal wasturned off. Consistent with the data shown in FIG. 4, the rat's painresponse is indicated by downward spikes. The baseline response 574 ahas a relatively large number of spikes, and the number of spikes beginsto reduce as the intensity of the modulation signal is increased (seeresponse 574 b in FIG. 5B). At the maximum therapy signal intensity, thenumber of spikes has been reduced to nearly zero as indicated byresponse 574 c in FIG. 5C. As the therapy signal intensity is thenreduced, the spikes begin to return (see response 574 d, FIG. 5D), andwhen the modulation signal is turned off, the spikes continue to return(see response 574 e, FIG. 5E). Significantly, the number of spikes shownin FIG. 5E (10-20 seconds after the therapy has been turned off) is notas great as the number of spikes generated in the baseline response 574a shown in FIG. 5A. These data are accordingly consistent with the humantrial data described above with reference to FIGS. 2A and 2B, whichindicated a beneficial effect lasting beyond the cessation of thetherapy signal. These data also differ significantly from resultsobtained from similar studies conducted with standard SCS. Notably,dorsal horn recordings during standard SCS treatments do not indicate areduction in amplitude spikes.

FIGS. 6A-6F illustrate animal response data in a rat model to adifferent noxious stimulus; in particular, a pinch stimulus 670. Thepinch stimulus is a mechanical pinch (rather than an electricalstimulus) at the rat's hindpaw. In each succeeding figure in the seriesof FIGS. 6A-6F, the amplitude of the therapy signal was increased. Thelevels to which the signal amplitude was increased were significantlyhigher than for the human study simply due to a cruder (e.g., lessefficient) coupling between the signal delivery electrode and the targetneural population. The vertical axis of each Figure indicates the numberof spikes (e.g., the spike-shaped inputs 372, 373 shown in FIG. 3) perbin; that is, the number of spikes occurring during a given time period.In the particular embodiment shown in FIGS. 6A-6F, each bin has aduration of 0.2 second, so that there are a total of five bins persecond, or 10 bins during each two-second period. The pinch stimulus 670lasts for three to five seconds in each of FIGS. 6A-6F. In FIG. 6A, thebaseline response 674 a indicates a large number of spikes per binextending over the duration of the pinch stimulus 670. As shown in FIGS.6B-6F, the number of spikes per bin decreases, as indicated by responses674b-674 f, respectively. In the final Figure in this series (FIG. 6F),the response 674 f is insignificant or nearly insignificant whencompared with the baseline response 674 a shown in FIG. 6A.

The foregoing rat data was confirmed in a subsequent study using a largeanimal model (goat). Based on these data, it is clear that therapysignals in accordance with the present technology reduce pain; further,that they do so in a manner consistent with that observed during thehuman studies.

Returning now to FIG. 3, it is expected (without being bound by theory)that the therapy signals act to reduce pain via one or both of twomechanisms: (1) by reducing neural transmissions entering the spinalcord at the dorsal root 393 and/or the dorsal root entry zone 387,and/or (2) by reducing neural activity at the dorsal horn 386 itself. Itis further expected that the therapy signals described in the context ofthe rat model shown in FIG. 3 operate in a similar manner on thecorresponding structures of the human anatomy, e.g., those shown in FIG.1B. In particular, it is generally known that chronic pain patients maybe in a state of prolonged sensory sensitization at both the nociceptiveafferent neurons (e.g., the peripheral nerve 385 and the associateddorsal root 393) and at higher order neural systems (e.g., the dorsalhorn neuron 383). It is also known that the dorsal horn neurons 383(e.g., the WDR cells) are sensitized in chronic pain states. The noxiousstimuli applied during the animal studies can result in an acute“windup” of the WDR cells (e.g., to a hyperactive state). In accordancewith mechanism (1) above, it is believed that the therapy signalsapplied using the current technology operate to reduce pain by reducing,suppressing, and/or attenuating the afferent nociceptive inputsdelivered to the WDR cells 383, as it is expected that these inputs,unless attenuated, can be responsible for the sensitized state of theWDR cells 383. In accordance with mechanism (2) above, it is expectedthat the presently disclosed therapy can act directly on the WDR cells383 to desensitize these cells. In particular, the patients selected toreceive the therapy described above with reference to FIGS. 2A-2Bincluded patients whose pain was not correlated with peripheral stimuli.In other words, these patients had hypersensitive WDR cells 383independent of whether signals were transmitted to the WDR cells 383 viaperipheral nerve inputs or not. These patients, along with the othertreated patients, experienced the significant pain reductions describedabove. Accordingly, it is believed that the disclosed therapy canoperate directly on the WDR cells 383 to reduce the activity level ofhyperactive WDR cells 383, and/or can reduce incoming afferent signalsfrom the peripheral nerve 385 and dorsal root 393. It is furtherbelieved that the effect of the presently disclosed therapy onperipheral inputs may produce short term pain relief, and the effect onthe WDR cells may produce longer term pain relief. Whether the reducedoutput of the WDR cells results from mechanism (1), mechanism (2), orboth, it is further expected that the high frequency characteristics ofthe therapeutic signals produce the observed results. In addition,embodiments of the presently disclosed therapy produce pain reductionwithout the side effects generally associated with standard SCS, asdiscussed further in co-pending U.S. patent application Ser. No.12/765,747, filed on Apr. 22, 2010, previously incorporated herein byreference. These and other advantages associated with embodiments of thepresently disclosed technology are described further below.

Certain of the foregoing embodiments can produce one or more of avariety of advantages, for the patient and/or the practitioner, whencompared with standard SCS therapies. Some of these benefits weredescribed above. For example, the patient can receive beneficial effectsfrom the modulation therapy after the modulation signal has ceased. Inaddition, the patient can receive effective pain relief withoutsimultaneous paresthesia, without simultaneous patient-detectabledisruptions to normal sensory signals along the spinal cord, and/orwithout simultaneous patient-detectable disruptions to normal motorsignals along the spinal cord. In particular embodiments, while thetherapy may create some effect on normal motor and/or sensory signals,the effect is below a level that the patient can reliably detectintrinsically, e.g., without the aid of external assistance viainstruments or other devices. Accordingly, the patient's levels of motorsignaling and other sensory signaling (other than signaling associatedwith the target pain) can be maintained at pre-treatment levels. Forexample, the patient can experience a significant pain reduction that islargely independent of the patient's movement and position. Inparticular, the patient can assume a variety of positions and/orundertake a variety of movements associated with activities of dailyliving and/or other activities, without the need to adjust theparameters in accordance with which the therapy is applied to thepatient (e.g., the signal amplitude). This result can greatly simplifythe patient's life and reduce the effort required by the patient toexperience pain relief while engaging in a variety of activities. Thisresult can also provide an improved lifestyle for patients whoexperience pain during sleep.

Even for patients who receive a therapeutic benefit from changes insignal amplitude, the foregoing therapy can provide advantages. Forexample, such patients can choose from a limited number of programs(e.g., two or three) each with a different amplitude and/or other signaldelivery parameter, to address some or all of the patient's pain. In onesuch example, the patient activates one program before sleeping andanother after waking. In another such example, the patient activates oneprogram before sleeping, a second program after waking, and a thirdprogram before engaging in particular activities that would otherwisecause pain. This reduced set of patient options can greatly simplify thepatient's ability to easily manage pain, without reducing (and in fact,increasing) the circumstances under which the therapy effectivelyaddresses pain. In any embodiments that include multiple programs, thepatient's workload can be further reduced by automatically detecting achange in patient circumstance, and automatically identifying anddelivering the appropriate therapy regimen. Additional details of suchtechniques and associated systems are disclosed in co-pending U.S.application Ser. No. 12/703,683, incorporated herein by reference.

Another benefit observed during clinical studies is that when thepatient does experience a change in the therapy level, it is a gradualchange. This is unlike typical changes associated with conventional SCStherapies. With conventional SCS therapies, if a patient changesposition and/or changes an amplitude setting, the patient can experiencea sudden onset of pain, often described by patients as unbearable. Bycontrast, patients in the clinical studies described above, when treatedwith the presently disclosed therapy, reported a gradual onset of painwhen signal amplitude was increased beyond a threshold level, and/orwhen the patient changed position, with the pain described as graduallybecoming uncomfortable. One patient described a sensation akin to acramp coming on, but never fully developing. This significant differencein patient response to changes in signal delivery parameters can allowthe patient to more freely change signal delivery parameters and/orposture when desired, without fear of creating an immediately painfuleffect.

Another observation from the clinical studies described above is thatthe amplitude “window” between the onset of effective therapy and theonset of pain or discomfort is relatively broad, and in particular,broader than it is for standard SCS treatment. For example, duringstandard SCS treatment, the patient typically experiences a painreduction at a particular amplitude, and begins experiencing pain fromthe therapeutic signal (which may have a sudden onset, as describedabove) at from about 1.2 to about 1.6 times that amplitude. Thiscorresponds to an average dynamic range of about 1.4. In addition,patients receiving standard SCS stimulation typically wish to receivethe stimulation at close to the pain onset level because the therapy isoften most effective at that level. Accordingly, patient preferences mayfurther reduce the effective dynamic range. By contrast, therapy inaccordance with the presently disclosed technology resulted in patientsobtaining pain relief at 1 mA or less, and not encountering pain ormuscle capture until the applied signal had an amplitude of 4 mA, and insome cases up to about 5 mA, 6 mA, or 8 mA, corresponding to a muchlarger dynamic range (e.g., larger than 1.6 or 60% in some embodiments,or larger than 100% in other embodiments). Even at the forgoingamplitude levels, the pain experienced by the patients was significantlyless than that associated with standard SCS pain onset. An expectedadvantage of this result is that the patient and practitioner can havesignificantly wider latitude in selecting an appropriate therapyamplitude with the presently disclosed methodology than with standardSCS methodologies. For example, the practitioner can increase the signalamplitude in an effort to affect more (e.g., deeper) fibers at thespinal cord, without triggering unwanted side effects. The existence ofa wider amplitude window may also contribute to the relativeinsensitivity of the presently disclosed therapy to changes in patientposture and/or activity. For example, if the relative position betweenthe implanted lead and the target neural population changes as thepatient moves, the effective strength of the signal when it reaches thetarget neural population may also change. When the target neuralpopulation is insensitive to a wider range of signal strengths, thiseffect can in turn allow greater patient range of motion withouttriggering undesirable side effects.

FIG. 7 illustrates a graph 700 identifying amplitude as a function offrequency for conventional SCS and for therapy in accordance withembodiments of the presently disclosed technology. Threshold amplitudelevel 701 indicates generally the minimum amplitude necessary to achievea therapeutic effect, e.g., pain reduction. A first region 702corresponds to amplitudes, as a function of frequency, for which thepatient senses paresthesia induced by the therapy, pain induced by thetherapy, and/or uncomfortable or undesired muscle stimulation induced bythe therapy. As shown in FIG. 7, at conventional SCS frequencies, thefirst region 702 extends below the threshold amplitude level 701.Accordingly, a second region 703 indicates that the patient undergoingconventional SCS therapy typically detects paresthesia, other sensoryeffects, and/or undesirable motor effects below the amplitude necessaryto achieve a therapeutic effect. One or more of these side effects arealso present at amplitudes above the threshold amplitude level 701required to achieve the therapeutic effect. By contrast, at frequenciesassociated with the presently disclosed technology, a “window” 704exists between the threshold amplitude level 701 and the first region702. Accordingly, the patient can receive therapeutic benefits atamplitudes above the threshold amplitude level 701, and below theamplitude at which the patient may experience undesirable side effects(e.g., paresthesia, sensory effects and/or motor effects).

Although the presently disclosed therapies may allow the practitioner toprovide modulation over a broader range of amplitudes, in at least somecases, the practitioner may not need to use the entire range. Forexample, as described above, the instances in which the patient may needto adjust the therapy may be significantly reduced when compared withstandard SCS therapy because the presently disclosed therapy isrelatively insensitive to patient position, posture and activity level.In addition to or in lieu of the foregoing effect, the amplitude of thesignals applied in accordance with the presently disclosed techniquesmay be lower than the amplitude associated with standard SCS because thepresently disclosed techniques may target neurons that are closer to thesurface of the spinal cord. For example, it is believed that the nervefibers associated with low back pain enter the spinal cord between T9and T12 (inclusive), and are thus close to the spinal cord surface atthese vertebral locations. Accordingly, the strength of the therapeuticsignal (e.g., the current amplitude) can be modest because the signalneed not penetrate through a significant depth of spinal cord tissue tohave the intended effect. Such low amplitude signals can have a reduced(or zero) tendency for triggering side effects, such as unwanted sensoryand/or motor responses. Such low amplitude signals can also reduce thepower required by the implanted pulse generator, and can thereforeextend the battery life and the associated time between rechargingand/or replacing the battery.

Yet another expected benefit of providing therapy in accordance with thepresently disclosed parameters is that the practitioner need not implantthe lead with the same level of precision as is typically required forstandard SCS lead placement. For example, while at least some of theforegoing results were obtained for patients having two leads (onepositioned on either side of the spinal cord midline), it is expectedthat patients will receive the same or generally similar pain reliefwith only a single lead placed at the midline. Accordingly, thepractitioner may need to implant only one lead, rather than two. It isstill further expected that the patient may receive pain relief on oneside of the body when the lead is positioned offset from the spinal cordmidline in the opposite direction. Thus, even if the patient hasbilateral pain, e.g., with pain worse on one side than the other, thepatient's pain can be addressed with a single implanted lead. Stillfurther, it is expected that the lead position can vary laterally fromthe anatomical and/or physiological spinal cord midline to a position3-5 mm. away from the spinal cord midline (e.g., out to the dorsal rootentry zone or DREZ). The foregoing identifiers of the midline maydiffer, but the expectation is that the foregoing range is effective forboth anatomical and physiological identifications of the midline, e.g.,as a result of the robust nature of the present therapy. Yet further, itis expected that the lead (or more particularly, the active contact orcontacts on the lead) can be positioned at any of a variety of axiallocations in a range of about T8-T12 in one embodiment, and a range ofone to two vertebral bodies within T8-T12 in another embodiment, whilestill providing effective treatment for low back pain. Accordingly, thepractitioner's selected implant site need not be identified or locatedas precisely as it is for standard SCS procedures (axially and/orlaterally), while still producing significant patient benefits. Inparticular, the practitioner can locate the active contacts within theforegoing ranges without adjusting the contact positions in an effort toincrease treatment efficacy and/or patient comfort. In addition, inparticular embodiments, contacts at the foregoing locations can be theonly active contacts delivering therapy to the patient. The foregoingfeatures, alone or in combination, can reduce the amount of timerequired to implant the lead, and can give the practitioner greaterflexibility when implanting the lead. For example, if the patient hasscar tissue or another impediment at a preferred implant site, thepractitioner can locate the lead elsewhere and still obtain beneficialresults.

Still another expected benefit, which can result from the foregoingobserved insensitivities to lead placement and signal amplitude, is thatthe need for conducting a mapping procedure at the time the lead isimplanted may be significantly reduced or eliminated. This is anadvantage for both the patient and the practitioner because it reducesthe amount of time and effort required to establish an effective therapyregimen. In particular, standard SCS therapy typically requires that thepractitioner adjust the position of the lead and the amplitude of thesignals delivered by the lead, while the patient is in the operatingroom reporting whether or not pain reduction is achieved. Because thepresently disclosed techniques are relatively insensitive to leadposition and amplitude, the mapping process can be eliminated entirely.Instead, the practitioner can place the lead at a selected vertebrallocation (e.g., about T8-T12) and apply the signal at a pre-selectedamplitude (e.g., 1 to 2 mA), with a significantly reduced or eliminatedtrial-and-error optimization process (for a contact selection and/oramplitude selection), and then release the patient. In addition to or inlieu of the foregoing effect, the practitioner can, in at least someembodiments, provide effective therapy to the patient with a simplebipole arrangement of electrodes, as opposed to a tripole or other morecomplex arrangement that is used in existing systems to steer orotherwise direct therapeutic signals. In light of the foregoingeffect(s), it is expected that the time required to complete a patientlead implant procedure and select signal delivery parameters can bereduced by a factor of two or more, in particular embodiments. As aresult, the practitioner can treat more patients per day, and thepatients can more quickly engage in activities without pain.

The foregoing effect(s) can extend not only to the mapping procedureconducted at the practitioner's facility, but also to the subsequenttrial period. In particular, patients receiving standard SCS treatmenttypically spend a week after receiving a lead implant during which theyadjust the amplitude applied to the lead in an attempt to establishsuitable amplitudes for any of a variety of patient positions andpatient activities. Because embodiments of the presently disclosedtherapy are relatively insensitive to patient position and activitylevel, the need for this trial and error period can be reduced oreliminated.

Still another expected benefit associated with embodiments of thepresently disclosed treatment is that the treatment may be lesssusceptible to patient habituation. In particular, it is expected thatin at least some cases, the high frequency signal applied to the patientcan produce an asynchronous neural response, as is disclosed inco-pending U.S. application Ser. No. 12/362,244, incorporated herein byreference. The asynchronous response may be less likely to producehabituation than a synchronous response, which can result from lowerfrequency modulation.

Yet another feature of embodiments of the foregoing therapy is that thetherapy can be applied without distinguishing between anodic contactsand cathodic contacts. As described in greater detail in U.S.application Ser. No. 12/765,790, incorporated herein by reference, thisfeature can simplify the process of establishing a therapy regimen forthe patient. In addition, due to the high frequency of the waveform, theadjacent tissue may perceive the waveform as a pseudo steady statesignal. As a result of either or both of the foregoing effects, tissueadjacent both electrodes may be beneficially affected. This is unlikestandard SCS waveforms for which one electrode is consistently cathodicand another is consistently anodic.

In any of the foregoing embodiments, aspects of the therapy provided tothe patient may be varied, while still obtaining beneficial results. Forexample, the location of the lead body (and in particular, the lead bodyelectrodes or contacts) can be varied over the significant lateraland/or axial ranges described above. Other characteristics of theapplied signal can also be varied. For example, the signal can bedelivered at a frequency of from about 1.5 kHz to about 100 kHz, and inparticular embodiments, from about 1.5 kHz to about 50 kHz. In moreparticular embodiments, the signal can be provided at frequencies offrom about 3 kHz to about 20 kHz, or from about 3 kHz to about 15 kHz,or from about 5 kHz to about 15 kHz, or from about 3 kHz to about 10kHz. The amplitude of the signal can range from about 0.1 mA to about 20mA in a particular embodiment, and in further particular embodiments,can range from about 0.5 mA to about 10 mA, or about 0.5 mA to about 4mA, or about 0.5 mA to about 2.5 mA. The amplitude of the applied signalcan be ramped up and/or down. In particular embodiments, the amplitudecan be increased or set at an initial level to establish a therapeuticeffect, and then reduced to a lower level to save power withoutforsaking efficacy, as is disclosed in pending U.S. application Ser. No.12/264,836, filed Nov. 4, 2008, and incorporated herein by reference. Inparticular embodiments, the signal amplitude refers to the electricalcurrent level, e.g., for current-controlled systems. In otherembodiments, the signal amplitude can refer to the electrical voltagelevel, e.g., for voltage-controlled systems. The pulse width (e.g., forjust the cathodic phase of the pulses) can vary from about 10microseconds to about 333 microseconds. In further particularembodiments, the pulse width can range from about 25 microseconds toabout 166 microseconds, or from about 33 microseconds to about 100microseconds, or from about 50 microseconds to about 166 microseconds.The specific values selected for the foregoing parameters may vary frompatient to patient and/or from indication to indication and/or on thebasis of the selected vertebral location. In addition, the methodologymay make use of other parameters, in addition to or in lieu of thosedescribed above, to monitor and/or control patient therapy. For example,in cases for which the pulse generator includes a constant voltagearrangement rather than a constant current arrangement, the currentvalues described above may be replaced with corresponding voltagevalues.

In at least some embodiments, it is expected that the foregoingamplitudes will be suprathreshold. It is also expected that, in at leastsome embodiments, the neural response to the foregoing signals will beasynchronous, as described above. Accordingly, the frequency of thesignal can be selected to be higher (e.g., between two and ten timeshigher) than the refractory period of the target neurons at thepatient's spinal cord, which in at least some embodiments is expected toproduce an asynchronous response.

Patients can receive multiple signals in accordance with still furtherembodiments of the disclosure. For example, patients can receive two ormore signals, each with different signal delivery parameters. In oneparticular example, the signals are interleaved with each other. Forinstance, the patient can receive 5 kHz pulses interleaved with 10 kHzpulses. In other embodiments, patients can receive sequential “packets”of pulses at different frequencies, with each packet having a durationof less than one second, several seconds, several minutes, or longerdepending upon the particular patient and indication.

From the foregoing, it will be appreciated that specific embodiments ofthe technology have been described herein for purposes of illustration,but that various modifications may be made without deviating from thepresent disclosure. For example, therapies described in the context ofparticular vertebral locations to treat low back pain may be applied toother vertebral levels to treat other types of pain. In still furtherembodiments, the therapeutic effect can include indications in additionto or in lieu of pain. Certain aspects of the disclosure described inthe context of particular embodiments may be combined or eliminated inother embodiments. For example, patients can receive treatment atmultiple vertebral levels and/or via leads or other signal deliverydevices positioned at multiple locations. The foregoing mechanisms ofaction are believed to account for the patient responses observed duringtreatment in accordance with the presently disclosed technology;however, other mechanisms or processes may operate in addition to or inlieu of the foregoing mechanisms in at least some instances. Further,while advantages associated with certain embodiments have been describedin the context of those embodiments, other embodiments may also exhibitsuch advantages, and not all embodiments need necessarily exhibit suchadvantages to fall within the scope of the present technology.Accordingly, the present disclosure and associated technology canencompass other embodiments not expressly shown or described herein. Thefollowing examples provide additional embodiments of the technology.

1. A method for establishing patient treatment parameters, comprising:selecting a neural modulation site to include at least one of a dorsalroot entry zone and dorsal horn of a spinal cord of the patient; andselecting parameters of a neural modulation signal to address a patientindication for a period of time after at least reducing an intensity ofthe signals, the period of time being at least one tenth of one second.2-25. (canceled)